Community Acquired Pneumoniae Lecture : Community Acquired Pneumoniae important Extra notes Doctors notes "لا حول ولا قوة إلا بالله العلي العظيم" وتقال هذه الجملة إذا دهم الإنسان أمر عظيم لا يستطيعه ، أو يصعب عليه القيام به .

Introduction to Pneumonia: Definition: it ​is an infection of the pulmonary parenchyma (the alveoli ) that causes inflammation, consolidation and exudation. Can be : Acute (fulminant) or chronic Histologically: Epidemiology: Common in winter Overall the rate of CAP 5-6 cases per 1000 persons per year Mortality 23% Pneumonia are high especially in old people Almost 1 million annual episodes of CAP in adults > 65 yrs in the US (1) (2) (3) Histological spectrum Fibrinopurulent alveolar exudate​is (Pus exudate that contains a large amount of fibrin) Mononuclear interstitial infiltrates​in Granulomas and cavitation​seen Happen in acute bacterial pneumonias. viral and other atypical pneumonias chronic pneumonias (happen in some TB cases)

Pathogenesis Two factors involved in the formation of pneumonia pathogens host defenses.

Pathophysiology : Inhalation or aspiration of pulmonary pathogenic organisms into a lung segment or lobe. Result from Secondary bacteraemia from a distant source, such as Escherichia coli urinary tract infection and/or bacteraemia (Less common) Aspiration of Oropharyngeal contents (multiple pathogens).

Classification of pneumonia : according to Risk factors: Age < 2 yrs , > 65 yrs (extreme ages) alcoholism ,smoking Asthma and COPD Aspiration Dementia (A chronic mental disorder marked by memory loss, personality changes, and impaired reasoning) prior influenza Immunosuppression ,HIV Institutionalization (The process of committing someone to a facility like prisons and mental hospitals) Travelling and staying in hotels: Legionella bacteria (بكتيريا المكيفات المركزية. تعيش في وحدات التكييف خصو ًصا في الفنادق وغرف العناية المركزة.) (waterborne transmission) pets, occupational exposures- birds C- psittaci = (Chlamydophila psittaci) Chronic lung & heart (S.pneumoniae) Classification of pneumonia : according to 1 3 Etiology (pathogen) 2 Clinical (Acquired enviroment) Anatomy

common cause of pneumonia in children less than 5 years 1- Pathogens: 4- Others 3- Viral pneumonia common cause of pneumonia in children less than 5 years 2- Fungal pneumonia 1- Bacteria (dominant) Atypical pneumonia Typical pneumonia Anaerobic Gram - Gram + 1)Parasites2)Protozoa 3)Chemical 4)Allergy ­1)Respiratory syncytial V. 2)Influenza V. ­ 3)Adenoviruses. ­ 4)Human metapneumovirus. ­ 5)SARS and MERS CoV. ­ 6)Cytomegalovirus. 7)Herpes simplex virus. ­1)Candida.  ­ 2)Aspergillosis.­ 3)Pneumocystis jiroveci ​(carinii), It causes PCP. 1)Legionnaies  pneumonia(Legionella) 2)Mycoplasma pneumoniae (most common) 3)Chlamydiophila  pneumoniae 4)Chlamydophila Psittaci ​ 5)Rickettsias.  ­ 6)Francisella tularensis  (tularemia) 1)Klebsiella pneumoniae 2)Hemophils influenzae 3)Moraxella catarrhal 4)Escherichia coli 1)Streptococcus pneumoniae (most common Typical pneumonia) 2)Staphylococcus aureus 3) Group A hemolytic streptococci 1)Streptococcus pneumoniae, H.influenzae and Moraxella: have cell wall therefore are gram stained and respond to Penicillin and B-lactam 2)Mycoplasma pneumoniae, Legionella and chlamydia: doesn’t have cell wall (resistant to drugs that work on cell wall E.g (penicillin and B-lactam) Parasites and protozoa infections are rare Immunocompromised patients are more likely to develop fungal + viral pneumonia

2- Anatomical pneumonia: 1-Lobar pneumonia Lobular 2-Bronchopneumonia Entire Lobe 3-Interstitial pneumonia

CAP and bioterrorism agents Bacillus anthracis (anthrax) Yersinia pestis (plague)  Francisella tularensis (tularemia) Coxialla . burnetii (Q fever) Level three agents

3- Classification by acquired environment: Community Acquired Pneumonia (CAP) Hospital Acquired Pneumonia (HAP) Nursing Home Acquired Pneumonia (NHAP) ImmunoCompromised Host Pneumonia (ICAP) Outpatient Inpatient Non-ICU ICU Streptococcus pneumoniae Mycoplasma / Chlamydophila H. influenzae, Staph aureus Respiratory viruses Legionella Staph aureus, Legionella Gram neg bacilli (Enterobacteriaceae, and Pseudomonas aeruginosa) H. influenzae

Community Acquired Pneumonia (CAP): Definition: Pneumonia acquired outside of hospitals or extended-care facilities for >14 days before the onset of symptoms. Streptococcus pneumoniae (most common) Haemophilus influenzae mycoplasma pneumoniae Chlamydia pneumoniae Moraxella catarrhalis Staph.aureus Commonly caused by Streptococcus pneumoniae , and drug resistant streptococcus pneumoniae (DRSP) is a major concern on this aspect.

Clinical presentation Treatment with penicillin Important What is the difference between typical and atypical community-acquired pneumonia? Typical Atypical Etiology S.Pneumoniae (Lobar Pneumoniae) H.influenza Moraxella catarrhal Mycoplasma pneumonia chlamydophila pneumoniae Legionella TB Viral, Influenza and Adenovirus or fungal Clinical presentation Sudden onset of fever, chill, productive cough, shortness of breath and chest pain. Rusty Sputum. Gradual onset headache, sore throat and body ache Gram stain Useful Useless (no cell wall) Radiography Lobar infiltrate Condolidation Dramatic changes: patchy or interstitial No Consolidation Treatment with penicillin Sensitive Resistant, treated with Macroides Diagnosis History & physical examination X-ray examination Laboratory : CBC- leukocytosis Sputum Gram stain- 15% Blood culture- 5-14% Pleural effusion culture Serology test X-ray liver enzyme high

Drug Resistant Strep Pneumoniae: Not Important Drug Resistant Strep Pneumoniae: 40% of U.S. Strep pneumo CAP has some antibiotic resistance: PCN, cephalosporins, macrolides, tetracyclines, clinda, bactrim, quinolones. All MDR strains are sensitive to vancomycin or linezolid; most are sensitive to respiratory quinolones. β-lactam resistance – Not for meningitis (CSF drug levels). PCN is effective against pneumococcal. Pneumonia at concentrations that would fail for meningitis or otitis media. For Pneumonia, pneumococcal resistance to β-lactams is relative and can usually be overcome by increasing β-lactam doses (not for meningitis!) PCN Minimum Inhibitory Concentration (MIC) mcg/mL to Streptococcus Pneumonmoniae: Susceptible Intermediate Resistant 2011CAP Guidelines MIC <2 4 MIC > 0.12 Meningitis MIC <0.06 --- MIC >0.12 PCN Minimum Inhibitory Concentration (MIC) mcg/mL to Streptococcus Pneumonmoniae: Susceptible Intermediate Resistant 2008 MIC ≤ 2 MIC = 4 MIC > 8 2007 CAP Guidelines MIC <2 --- MIC > 2 Meningitis MIC <0.06 MIC >0.12 Boys slides Girls slides Pneumococcal CAP: Be cautious if using PCN if MIC >4. Avoid using PCN if MIC >8. Remember that if MIC <1, pneumococcus is PCN-sensitive in sputum or blood (but need MIC <0.06 for PCN-sensitivity in CSF).

Atypical Pneumonia Organisms that cause Atypical Pneumonia: Chlamydia pneumonia Mycoplasma pneumonia Legionella spp Psittacosis – Parrots (Caused by birds droplets) مرض الطيور Coxiella burnettii (Q fever) مرض الماعز Viral (Influenza, Adenovirus) AIDS PCP TB (M. intracellular) About Atypical Pneumonia: Approximately 15% of all CAP(Community-Acquired Pneumonia) Not detectable on gram stain Won’t grow on standard media Often extra-pulmonary manifestations: Mycoplasma: otitis, non-exudative pharyngitis, watery diarrhea, erythema multiform, increased cold agglutinin titer Chlamydophilla: laryngitis Most don’t have a bacterial cell wall Don’t respond to β-lactams Therapy: macrolides, tetracycline, quinolones (intracellular penetration, interfere with bacterial protein synthesis)

Mycoplasma pneumonia: ● Eaton agent (1944). ● No cell wall. ● Common. ● Rare in children and older than 65 years. ● People younger than 40. ● Crowded places like schools, homeless shelters, prisons. ● Usually mild and responds well to antibiotics. ● Can be very serious. ● May be associated with a skin rash, hemolysis, myocarditis or pancreatitis. Mycoplasma pneumonia x-ray Mortility Rate 1.4% - Detection through serum antibodies - Low mortality rate

Chlamydophila pneumoniae Chlamydia Pneumonia: Chlamydophila pneumoniae is a species of Chlamydophila, and it’s Obligate intracellular organism 50% of adults sero-positive Mild disease Sub clinical infections common 5-10% of community acquired pneumonia This atypical bacterium commonly causes pharyngitis, bronchitis, coronary artery disease and atypical pneumonia in addition to several other possible diseases. Chlamydophila pneumoniae وجه الشبه بين مايكوبلازم و الكالميديا: عدم وجود الجدار الخلوي، لا يصيب كبار السن والأطفال، لا يسبب حالات خطيرة (غالبًا). وجه الاختلاف بين الاثنين (مهم جدًا): المايكوبلازما تسبب طفح جلدي وأمراض في القلب والبنكرياس، بالإضافة لأماكن العدوى.

Psittacosis: Q Fever: -Chlamydophila psittaci -Exposure to birds Important Psittacosis:  -Chlamydophila psittaci  -Exposure to birds -Bird owners, pet shop employees, vets Parrots, pigeons and poultry (الدواجن). -Birds often asymptomatic (because it is normal flora for them). 1st: Tetracycline Alt: Macrolide Q Fever: Coxiella burnetti Exposure to farm animals mainly sheep ماعز 1st: Tetracycline, 2nd: Macrolide

Symptoms : Signs : Legionella pneumophila: -Insidious onset -Mild URTI (upper resp tract infection) to severe pneumonia -Headache -Malaise -Fever -Dry cough -Arthralgia (pain in a joint)/ myalgia(pain in a muscle) Signs : -Minimal Few crackles -Rhonchi (rattling sound of the lung خشخشة) -Low grade fever Legionnaire's disease. Serious outbreaks linked to exposure to cooling towers ICU admissions. Hyponatremia common (<130mMol) (low sodium) Bradycardia WBC < 15,000 Abnormal LFTs (liver function test) Raised CPK (creatine phosphokinase) Acute Renal failure Positive urinary antigen

Cont… Diagnosis: Treatment: -Culture on special media BCYE -CBC Mild elevation WBC -U&Es -Low  serum Na (Legionella) -Deranged LFTs = Increase Liver enzymes ↑ ALT (Alanine transaminase enzyme) ↑ Alkaline phosphatase -Culture on special media BCYE (لكن عمليا ما يسوونه لانه يطول اكثر من اللازم) -Cold agglutinins (Mycoplasma) -Serology -DNA detection Differential diagnosis :(ما ركز عليها) -Pulmonary tuberculosis -Lung cancer -Acute lung abescess -Pulmonary embolism -Noninfectious  pulmonary infiltration Treatment: Macrolide (Erythromycin) Rifampicin Quinolones Tetracycline Treat for 10-14 days (21 in immunosuppressed)

Importance of history taking in patient with community-Acquired pneumonia: Solid organ transplant Any pathogen Bacterial , viral, fungal,or parasitic HIV Pneumocystis jeroveci Travel to some area in USA Endemic Mycosis Exposure to air-conditioning, cooling towers, hot tub, hotel stay, grocery sore mist machine Legionella pneumophilla Exposure to Turkeys, chickens, ducks or parrots Chlamydia psittaci Exposure to contaminated bat caves Histoplasma capsulatum Exposure tosheep, goat or cattle Coxiella burnetii Exposure to rabbits Francisella tularensis Occupation Mycobacterium tuberculosis, HIV Evaluate the severity & degree of pneumonia: Is the patient will require hospital admission? patient characteristics comorbid illness physical examinations basic laboratory findings

Diagnosis: -no culture -urine test is used Sputum Gram stain- 15% Sputum culture Bronchoscopic specimens Blood culture 6-10% NP swab for respiratory viruses Legionella urine antigen Serology for M.pneumoniae, C.pneumoniae Cold agglutination M.pneumoniae More Invasive procedure in sick patient Only in girls slides Physical examination: Respiratory signs on consolidation Other systems Chest x-ray examination Laboratory: CBC- leukocytosis Electrolytes (↓Na in legionella) Urea, creatinine, LFT

Antibiotic Treatment: Management: Girls slides Outpatient or inpatient (hypotension, confusion and oxygenation) and age Previous treatment in the past 3 months Resistance patterns in the community Boys slides Outpatient, healthy patient with no exposure to antibiotics in the last 3 months Outpatient, patient with co-morbidity or exposure to antibiotics in the last 3 months Inpatient : Not ICU Inpatient : ICU Antibiotic Treatment: Macrolide: Azithromycin, Clarithromycin Doxycycline Beta Lactam :Amoxicillin/clavulinic acid, Cefuroxime Respiratory Flouroquinolone:Gatifloxacin, Levofloxacin or Moxifloxacin Antipeudomonas Beta lactam: Cetazidime Antipneumococcal Beta lactam: Cefotaxime

Macrolides Doxycycline Levofloxacin B-lactam And Macrolide B-lactam And Outpatient, healthy patient with no exposure to antibiotics in the last 3 months S pneumoniaes, M pneumoniae, Viral Outpatient, patient with comorbidity or exposure to antibiotics in the last 3 months C. pneumoniae, H influenzae M.catarrhalis anaerobes S aureus Inpatient : Not ICU (not important) Same as above +legionella Inpatient : ICU (not important) Same as above + Pseudomonas Summery: Macrolides and Levofloxacin = are effective for both Typical and Atypical B-lactam only work on Typical therefore need to be combined with Macrolides in the exam they may ask about the antibiotic that covers the typical and nontypical bacteria (important)

The diagnostic standard of severe pneumonia: not important (It means : the problems that a severe pneumonia patient will have) 1-Altered mental status 2-Pa02<60mmHg. PaO2/FiO2<300, needing MV 3-Respiratory rate>30/min 4-Blood pressure<90/60mmHg 5-Chest X-ray shows that bilateral infiltration, multilobar infiltration and the infiltrations enlarge more than 50% within 48h. 6-Renal function: (Under <20ml/h) and (Under<80ml/4h)

Notes: Complications: prevention Not Important Normal respiratory rate is 12-16 -PaO2/FiO2 ratio. The ratio of partial pressure arterial oxygen and fraction of inspired oxygen, sometimes called the Carrico index, is a comparison between the oxygen level in the blood and the oxygen concentration that is breathed. Complications: 1-Death 10% , 40% (ICU) within 5 days 2-Mainly old age with sever pneumonia 3-Respiratory and cardiac failure 4-Empyema 10% prevention By giving Vaccination : Influenza S.pneumoniae Prevention of Aspiration by: Head Position Teeth cleaning

Community Acquired Pneumonia not common in young Young have twice Pneumonia within 3 months is an immunocomprmised and suspect HIV Young travelled also suspect HIV Anthrax and Coxiella (Q fever- ماعز) cause Pneumonia. Anthrax is a deadly disease Liganella come from hot water, hospital fountain, aircoditioning Have High fever, don’t respond to Penicillin and effect old and immunocomprmised patient Good sputum have: Macrophages, WBC, Columnar ciliated epithelial cells (No Squamous cells) Mycoplasma and chlamydia : we don’t do culture , we do PCR and serology (because it require living cell wich takes time patient would be already dead)

MCQs: 1-The most common organism that causes Atypical pneumonia ? A- Klebsiella pneumonia B- Legionella C- Mycoplasmal pneumonia D- Ricketsias 2-Patient came with productive cough , shortness of breath and chill , which organism could cause these symptoms ? A- Legionnaires pneumonia B- adenovirus C- M. tuberculosis D- H. infleunza 3-What possible drug you could prescribed for a patient who has Mycoplasma pneumoniae ? A- Penicillin G B-Erythromycin C- ceftriaxone D- cephalexin 3-B 2- D 1- C

SAQ: 1-A patient have been admitted to the ICU suffer from fever. what is the most common micro-organism causing this? 2- what will you do to confirm the diagnosis? 3-How will you treat this condition? 4- Sara had a flu tow days ago, now she suffers from diarrhea, otitis, and erythema. what is the diagnosis? 5- List the possible causative agents and the micro-organisms for the diagnosis above? 1- legionella pneumophila 2- CBC, Mild elevation WBC, U&Es, Low  serum Na, Deranged LFTs, ↑ ALT (Alanine transaminase enzyme), ↑ Alkaline phosphatase, Culture on special media BCYE, Cold agglutinins (Mycoplasma), Serology DNA detection 3- Macrolide (Erythromycin), Rifampicin, Quinolones, Tetracycline, Treat for 10-14 days (21 in immunosuppressed) 4-Atypical pneumonia 5- Chlamydia pneumonia, Mycoplasma pneumonia, Legionella spp, Psittacosis, Coxiella burnettii

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